In the Bubble with Andy Slavitt: Our Shot

Exclusive: FDA Commissioner on COVID-19 Vaccine for Kids 0-5 (with Robert Califf)

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Description

Many parents with young children have one question: When will my kid be eligible for a COVID-19 vaccine? They got one step closer to an answer this week, when Moderna filed an Emergency Use Authorization for a vaccine the company says is safe and effective for kids ages 6 months through 5 years. FDA Commissioner Robert Califf tells Andy what’s holding up approval, why getting the dose right is so critically important, and whether rumors that the FDA would wait for data on a three-dose vaccine from Pfizer before clearing a two-dose vaccine from Moderna are true.

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Transcript

SPEAKERS

Andy Slavitt, Robert Califf

Robert Califf 

When we get it, we’ll have to look at it. And we’ll move as quickly as we can. And when I say we, again, I’m not talking about me, I’m talking about the same people that have guided us through the last two years, I think quite admirably.

Andy Slavitt

Welcome to IN THE BUBBLE. This is your host, Andy Slavitt. With a breaking news edition, the voice you just heard was FDA commissioner, Rob Califf, who gave us an exclusive interview that we are posting today. We’re posting it early because of the news today that Moderna just filed its EUA for kids zero to five. And that’s one of the major topics that Rob and I get into it is a great interview. I think you will hear Rob’s response to the question of, of what comes next. You know, there has been a lot of controversy and a lot of swirl about whether or not the FDA is going to delay, its review, whether it’s not going to delay its review, I want to give you a chance to hear Rob, address that directly, we get into a very deep in-depth conversation, I call him putting him in the dental chair to some degree on this. And then afterwards, I we talk a little bit after the interview about my own interpretation of what he said in what comes next for the kids, zero to five. Now you may be listening to this very much, because this is the topic of the day. And I’m pleased that in the bubble can bring it to you quickly. But I want you to know that there is a lot more to this conversation with Calum that I hope you listen to. He is an extraordinary public health figure with extraordinary perspective. And there are some things that he says in here that related to kids zero to five, that are really important to pay attention to, he talks about misinformation, he talks about some real perspective on fighting this pandemic, he talks about other major issues and that are affecting our health. And he says some really profound things.

Robert Califf  02:16

Like the big alarm going off right now for me, in addition to everything else is that we’ve seen this decrease in life expectancy across the US while before the pandemic. So much so that after the effect of the pandemic, we just hit the five-year mark, that is Americans live five years shorter than the average of other high-income countries. And while COVID has been a significant part of it, the majority is actually the thing she didn’t mention because we tend to take them for granted. Heart disease is number one, chronic lung disease very high up there. Renal dysfunction, depression, and suicide is a huge factor. And of course, we have the overdose and death problem

Andy Slavitt

The other thing that I want to play one more clip for you before we get into the interview with Rob, is he offers some extraordinary perspective and how far the science has come. And he makes an extraordinary statement that I want you to hear. And I want to pull it out for you about what the effectiveness of the vaccines and antivirals actually means for us.

Robert Califf

If you get vaccinated, your chances of dying from COVID are reduced by 90%. If you’re unlucky enough to get infected, even though you’re vaccinated, if you get an antiviral, your risk of dying is reduced by yet another 90%. Now, most people listening are probably not mathematicians. But this is a contingent probability, it means that almost no one should be dying from COVID. At this point if we optimally deployed vaccination and antivirals, so it’s a tragedy.

Andy Slavitt  04:01

Almost no one should be dying from COVID at this point. And yet we have hundreds of people in the US and still 1000s around the globe, still dying from COVID. What this tells us is it sciences kind of […] the society and our society’s response to the science. That’s an extraordinary place to be. And I think with the approval of vaccines from kids zero to five, which under any circumstance appears, is going to happen within the next number of weeks, we’ll be able to say that for virtually everybody in the country. It’s not to say that people who aren’t frail will be more deeply affected by a virus. But that’s the majority place to be and I think you’ll love Rob’s perspective, or I love Rob’s perspective. I hope you appreciate it too. Even beyond the news of that we’re gonna jump right into kids zero to five. You’ll see the interview starts as we get into his return to FDA. And it’ll quickly pivot towards what’s in front of the FDA now, we recorded the interview just before the submission from Moderna. So you might hear that in the Tensas. We talked about when Moderna submits, Madonna has now submitted an EUA for kids zero to five. So here goes, I hope you enjoy it.

Andy Slavitt

And hey, Rob, how you doing? Having a good day?

Robert Califf 

I am having a as good as day as you can have as FDA commissioner.

Andy Slavitt

How does it feel to be back at the FDA, this is your second tour duty.

Robert Califf 

It feels good to be back. You know, I had a as you know, a very interesting time when I was here, the first time through, but it was relatively short, there was an election outcome that was unexpected. You and I used to eat dinner, and lament the bad parts and talk about the good parts and aspiration. So you know, I hadn’t planned on coming back. But when the call came, there certainly were things I hoped I could accomplish. And as you also know, the mission is unparallel to try to improve things for the good of the American people. And now at age 70, I got to think about my grandkids, what kind of world are they going to going to be in so the one other thing to mention, which is so important is perhaps not surprisingly, probably 80% of the leadership, two or three levels down at FDA is the same as it was. So despite all the trials and tribulations since the last left, people are very dedicated to their work here. And that’s a very positive environment to work in.

Andy Slavitt

Does it feel different the second time around? I mean, obviously, we’re in the midst, or hopefully, the tail end of a pandemic. And that’s got to feel very different, but feel different just coming back being back? Or was it just like you never left?

Robert Califf  06:58

Yeah, there’s a little bit different, I hope I’m wiser, I have a better understanding of how to get things done, and when to pick something to try to get done and when to leave something alone. So I’m hopeful I’ll be more effective this time around.

Andy Slavitt

You know, you and I both joined the Obama administration and the later side, both in the second term, we served together, as you said, we became friends. So you know, it’s always a little bit interesting when I do this show and interview people that I know so well, and that I’m so fond of, there’s a lot of things on people’s minds around the FDA, that I’m going to have to ask you. So I’m going to put some challenging questions to you. But I want people to know that we’ve got this relationship. So it’s important that that we have real conversation about some of the things that you see going on, and some of the biggest opportunities that I would start at the kind of highest level Rob, you know, while you still got your big picture hat on as you’ve come in, and you’ve had some perspective, and some distance, we’ve just experienced with gotta be an exceptional set of breakthroughs in science, at record pace, the development of the mRNA vaccines, and the other vaccines for COVID, as well as the relatively rapid deployment of therapeutics and other related bio technologies. And this is a development process that if people who know how long it normally takes for a drug to be developed, or a vaccine to be developed, can be seven to 10 years or longer. Yet, we’ve just seen great vaccines, hitting complicated targets, and the therapeutics and so forth, happen. And I guess it leaves people and leaves me wondering, I wonder if it leaves you wondering, you know, what, what can we do to make this more of the norm, rather than the exception?

Robert Califf  08:59

Well, as you correctly imagine, I’ve thought about this a lot. But while it’s an extraordinary example, it’s not the first time. And I think the principles are unchanged. I think in America, whenever we prioritize something across sectors, and we have a common objective, and we agree, it’s a common objective. And we agree to work across those boundaries as a means of doing business. That’s when we’re most effective. And you know, we can point to times in our history, whether it was war, or you know, dealing with the great recessions, all those sorts of things. When we agreed to work together, we can really get things done. We also had a little bit of luck, as you know, there was no guarantee that these vaccines were going to be so good. But, you know, luck, as the old saying goes, tends to fall in the favor of those who are prepared.

Andy Slavitt

Yeah, and we’ll talk about some of those things and you know, we had this, we have this term emergency use authorization, which is to say, hey, guys, it’s an emergency, there’s lots of people dying. So let’s get on to more time funding. And, you know, it makes me think, like, the promise of the mRNA platform, as we heard last week on the show, is a possibility to create a 90% effective flu vaccine, possibility to create vaccines or therapeutics that target certain cancers, and HIV and even diabetes. Now, those things may seem far off, but count me as greedy. Count me as saying, boy, if we can make those things happen in three years, not seven, or, you know, a year instead of two, we should do everything we can. And maybe this is an emergency, you know, maybe we should think of it as an emergency. Because of all the people that every year are dying from HIV and from flu and from cancer. Do you look at examples like that, and say, boy we got to have a sense of urgency and figure out how to bend the rules, break the rules, work together, almost stay on war footing to make that happen?

Robert Califf

Well, what person faced with a serious illness with disability or death, wouldn’t see it as an emergency. So I think we should, also as much as we can, but we also need to have a healthy respect for the fact that most things that we try don’t work. Remember that 90% of drugs that make it into phase one, that’s after many, you know, that’s a small fraction of those that were somebody’s best idea that never made it through preclinical testing, but 90% of those that make it to phase one don’t make it to market because the risks outweigh the benefits. So there’s some things that we have to do with due process and careful measurement. And when it’s not a home run, like these vaccines were, it gets really complicated, and you gotta have good evidence to back you up.

Andy Slavitt

Sure. So you know, I’m really excited about this, as you know, I mean, first of all, I was in an intensive care unit doctor, so I don’t get really excited about anything. It’s more, you know.

Andy Slavitt  12:04

So but to the extent that you see something promising, and it’s in that 10% of categories, that makes it through phase one, and it is in one of these areas, like heart disease, like depression, where, you know, lives can be saved. Do you feel like FDA could get in the path where the norm can be the sort of accelerated, you’re talking to America now, who I think has a taste of what’s possible. And, you know, I think this is a real potential positive story. If we could say, coming out of the pandemic, you know, we lost a million lives in the US. But we’re gonna go save a million lives that would otherwise be saved, because we have the ability to do some pretty extraordinary things.

Andy Slavitt

Oh, I could see your enthusiasm.

Robert Califf

But you know, that’s why I’m a big fan of accelerated approval. There’s one example. You know, my mom had multiple myeloma in her 80s. And, you know, they were making a decision to go with comfort care when I call red pasture. This is when I was commissioner and said, hey, what’s got anything new? And he said, we just approved a drug from refractory multiple myeloma based on an accelerated basis. And it gave her three or four years of additional good life. So I saw it for real, but, at same time, I’d say we have to be really sober about what it takes to not only accelerate things, but to be sure that we’re right. So over half the drugs now approved by the FDA are accelerated.

Andy Slavitt

Which means what? Accelerated means approximately how many years from start to finish?

Robert Califf 

No one can say for sure, but it’s at least a couple of years. So rather than requiring that you prove that your drug has a benefit that outweighs the risk, the requirement is that you have a mark or a biomarker, which is not proven, but which the FDA deems is reasonably likely to have benefits outweigh risks. And then Americans have told their congress people, we would rather take more risk and have earlier access. That’s happening. The problem we’ve got right now is we haven’t fulfilled the second part of the bargain, which is okay, your drug goes on the market, but then you’ve got to figure out is the likelihood gonna be confirmed in the real world, and that’s where a lot of work is currently being done. And I’d really stress out as being critically important for us.

Andy Slavitt  14:52

Well, the one truism that I learned is that the FDA is 100% of the time we’re going to get criticized for its decision for either being too fast or too slow. And in some cases, both too fast and too slow, is harder that is to believe. And it depends on where we sit. And it depends on situation but yet I think, looking for these wins, where you could say we can accelerate by two years, that’s a lot of life saved. Let me move to a different topic. And this is where I’m going to put you in the dentist’s chair a little bit. By the way, you should know, Robert, today’s the day when I’m going to the dentist twice in the same day, wants to periodontist and wants to an orthodontist. So that accounts for my wonderful mood, I’m sure.

Robert Califf

Bad choice of days for me.

Andy Slavitt 

So I would put you in a dental chair to talk about, I’d say maybe one of the most last outstanding topics that people are still passionate about, and that’s vaccines for kids zero to five. And I think parents have a lot of very reasonable questions. You know, it remains the one major gap in our vaccine coverage. I think we’re about 18 months now after the first emergency use authorization. And it’s the last age group that hasn’t been filled. And, you know, it took us nine months to develop the vaccine. And it’s taken us twice as long as six to 18 months, and we still don’t have vaccines for kids there to five, what is what has been the core problem?

Robert Califf 

Well, first of all, I mean, let me just register that I’m a grandparent of two grandchildren who are less than age five. So I completely understand the issue and the anxiety. But I learned a lot about this 25 years ago, when we first started really addressing the issue of medications in children in a really serious way up until then, for the most part, medicines were developed in adults. And then it was sort of assumed that a child was just a smaller adult, which is completely wrong. And there were a lot of hard work of many pediatricians. And I was able to, you know, glad to be able to help with this. We got a law set of laws passed that required that testing be done in children to figure out the right dose, because oftentimes, the best guess, about the right dose, when applied to a child turns out to be wrong. And the risks can outweigh the benefits and toxicities can occur because of this. And so that the fundamental issue is that very young children are very different than adults. And the testing requires very careful evaluation of dosing. And usually that’s done by figuring out the dose than an adult and then working your way down in shoulder of being as close to parallel as you can be. But Let’s also not forget that those who volunteer for the trials at age zero to five are parents volunteering their children, for an experiment for the benefit of all other children. And so it didn’t come out right at first, it’s taken more work than expected. And so it’s taken longer than expected.

Robert Califf  16:38

One of the things that’s happened, of course, in the intervening time that that’s a good explanation is we had delta and Omicron. And delta and Omicron have made the vaccines less effective at preventing infection for all age groups, right, are kids zero to five unfairly penalized in the sense that their trials were going on at the time when effectiveness was down for everybody. And of course, we didn’t pull vaccines off the market when they became less than 50% effective at presenting preventing infection in slightly older age groups. So did they get caught in some sort of inadvertent trap? And that their trials were just conducted at the time when we had these variants that have just made the vaccines less effective, still important for serious illness but much less effective at preventing infection?

Andy Slavitt  18:15

I don’t think so, Andy, because, you know, the remit of the FDA, and I hope what any parent will want for their child is an evaluation of the benefits and the risks. And of course, you know, it’s publicly known we are poised to entertain an application from at least one of the manufacturers where they’ve said in a press release that their efficacy is Around 40%. So we’re just waiting on that application to come in. It’s not there yet.

Andy Slavitt 

So it’s 40%, something that would be approved?

Robert Califf 

One of the as you well know, Andy, one of the most important things about the commissioner, in terms of the way things work in public policy is the Commissioner doesn’t make the decisions about individual products, because I’m a political appointee. The center director is where the buck stops on that.

Andy Slavitt 

So you can’t say what would happen. But what I don’t hear you saying is that you would rule out approving a 40% effective vaccine, that’s below a standard that could ever be approved.

Robert Califf  20:40

I think that’s entirely fair to say. And it’s this product of many discussions with advisory committees and public statements by Peter marks and his team, it’s really always a matter of weighing the benefits and the risks, the benefits outweigh the risks, then, you know, the green lights.

Andy Slavitt 

Likely to go, and so far, at least, we haven’t heard of any risks being reported, um, you can’t say until the data is submitted, I understand.

Robert Califf 

Well, well, hold on, hold on. We haven’t heard of any specific risks in children that are different than the risks and adults. I mean, there are allergic reactions, there are side effects, there is the issue of myocarditis, all of which has to be carefully evaluated. And, again, I’ll just report, something that that I find fascinating. There were a whole series of drugs that got all the way through adults, got all the way through their patent life, you know, after 13 years and became generic, where no one knew the right dose and children, the NIH formed a network to evaluate those drugs, and over 100 have had their labels change. When the studies were done, the dose was wrong and children. And so, you know, I think, unfortunately, there’s been a view that it’s a matter of a company submitting their data, and the next day without doing anything else, we make a decision. We’ve actually got to have the raw data, because we perform a service for the US in the world of doing the analysis independently of the company. Companies are full of good people. But there is a financial interest there that has to be considered.

Andy Slavitt  22:24

That makes sense. I think that, you know, there was an article in Politico, which you and I have discussed, that sort of, I would say, questioned, not the process at the FDA, but question the urgency of the FDA that the FDA wasn’t implying the same level of urgency that it applied to others. So for example, it pointed to the fact that Moderna was planning or reporting that they’re going to submit data in May to the FDA or an application. And this article from Politico said that the FDA was thinking about waiting until it had another application in from Pfizer, for either simplicity, or some reasons that pointed to it, didn’t actually quote any but if the FDA, so it felt to me, fiery it for me to criticize politico, but I’m going to criticize Politico and say, sometimes they look for controversy, or they try to drum up something. But I’m wondering if you could speak to that. Is there truth to that? Or is it, and again, I’m not saying the next day, there’s an approval, but I’m asking is, is there any reason why FDA would wait, if it received an application?

Robert Califf

Categorically, there’s no reason for the FDA to wait. I mean, these are the same people that have been working for two years, show me a time when people have said, you know, once it was all said and done, that they waited too long. And this is no different. I mean, FDA, remember, we don’t have any application. We don’t have any data at this point. When we get it, we’ll have to look at it. And we’ll move as quickly as we can. And when I say we, again, I’m not talking about me. I’m talking about the same people that have guided us through the last two years, I think quite admirably yet are all sorts of things discussed about potential for this or that. As we’re thinking about our strategy, of course, all sorts of things are discussed. And I think it’s just disappointing that gossip like this would appear in what should be a reputable political discourse.

Andy Slavitt

Yeah. I’m glad you had a chance to clarify that. And it sounds like what you’re saying is that the FDA is policy it will be to have a brochure with the same sense of urgency you did with adults to schedule the meetings to review as quickly as possible and make an approval as quickly as possible if the data that is suggested should be approved.

Robert Califf 

And making sure that we do it right.

Andy Slavitt  24:55

Just a couple more questions on this topic. Then we’ll get lunch out of the dentist’s chair I want to take a couple of other angles on this question for a second. And they’re going to limit you probably say I’m wrong in all cases. But let me just take a shot at these things. Are we looking at the wrong endpoint when we look at infections? In other words, could we be looking? Or should we be looking at this as a situation? Let’s say kids with serious illness, who are most at risk, and we were looking at the endpoint of death, or hospitalization? If that were the goal, we were looking at the vaccine under those auspices, would we approach it any differently?

Robert Califf 

it would actually be more difficult because you would need very, very large sample sizes to prove that any result you found was not due to the play of chance. And so looking at infections is a way to reduce your sample size, assuming that if you reduce infections, you’re also going to reduce hospitalizations, and death. Death is so although when any child dies, it’s a major tragedy. Death is rare enough that you would need very, very large sample sizes to prove a reduction in death.

Andy Slavitt  26:09

About hospitalization, is there is that, is it feasible to say, to run a trial? And look, this may be Monday morning quarterbacking maybe too late but maybe, or is it possible to say this should be approved for kids with serious illness as soon as possible and there are cases, and I’m trying to find those cases, this example where the benefits so clearly outweigh the risks with certain individuals.

Robert Califf  26:34

I think you’re raising a hypothetical there that you have a dose which is effective, which we just don’t have, and for the same hospitalization as an outcome is even more difficult than death in this regard, because the children who are most likely to be hospitalized have other illnesses, and so they do deserve special care. But if they come to the hospital, knowing whether it’s COVID that caused it or their underlying illness, you know, Asthma is a classic example. That can be very difficult to sort out. And, you know, I’ve spent years doing clinical trials and trying to adjudicate the meaning of things that happened to people, you know, what was the underlying cause? It’s, it introduces an element of uncertainty. I think the trials are fundamentally sound, the great breakthrough, Andy would be if we had a surrogate marker, like we have for HIV, and hepatitis C, which is viral load, you’re gonna see some very interesting data related to the viral, the measured viral load in COVID, in the near future. But suffice it to say that we don’t have adequate data right now to use a surrogate. And that is very frustrating

Andy Slavitt 

if you determined that the vaccines were safe, and but if the FDA staff distributed, that they were safe. And given that there’s three doses and potentially being approved for at least Pfizer, it felt like in January, February, the FDA and I realized this is before your time there was contemplating some earlier approval, when there was work still being done on the third dose? Is it ever? Is it ever a universe of possibilities for creative things that happen in situations like this, such as approving the regimen to begin? Before everything’s completely bagged, or in certain situations, saying to parents, it’s okay to take it off label in smaller doses? And say, Germany is allowing some off label use among kids? Is there any other kind of creative things? These are things that parents, you know, trying to figure out how is there a way through the system in the most dire of cases.

Robert Califf  28:49

There is tremendous latitude given to the FDA in the setting of a public health emergency, as you know, to make decisions but recommending an unknown dose to a child who’s otherwise sick where the potential toxicities have not been quantified, just doesn’t fit in, at least for my view into something the FDA should be doing. And we’ve also got to make sure that the parents who are hesitating right now get convincing evidence and that we do everything possible to protect their children. And hopefully, we will get to an answer fairly soon now.

Andy Slavitt 

Thanks for going through all that. I think people will be pleased to see the urgency and your explanation of the issues. You know, doesn’t mean everybody’s always going to be happy and I think you, in your job, you’re pretty much aware that very rarely are people ecstatically happy. Look, I thought I had a tough job but I don’t know if I could have ever stomach. Some of the things that FDA has to deal with just but you basically parents or family members begging for with a called compassionate use of medication at a time when they’re out of hope, and this is the last straw they’re clutching to, and having to make decisions like that. It’d be very, very, very hard to do. And I always admired and those decisions and was always grateful that I didn’t have to make them.

Robert Califf 

Well. Keep in mind, as I said, I was an ICU doc, and you frequently make decisions like that in very tough circumstances. And like I say, the internal compass is important. And by the way, you did withstand a lot of attacks in the job you were in. A lot.

Andy Slavitt  30:41

Yeah, that’s probably true.

Andy Slavitt

Let’s move on to some other pandemic topics, and then maybe get a couple of other things that the FDA is involved in. Both Moderna and Pfizer have been talking publicly, in fact, so is the external FDA committee about potential for a Bi-vaillant vaccine is when to be potentially ready for the fall or winter. Can you talk a little bit about that? That seems to be where we’re headed without committing to things you haven’t seen data on yet. Is that a sensible thing for people to be talking about publicly?

Robert Califf 

Well, as you know, we had an advisory committee meeting recently that was not about an individual product, but to try to set the landscape for the fall when I think most prognosticators expect we’ll be in for another surge next winter unless we prepare for it in the fall. So we wanted to sort of see if there was agreement on how to proceed. There are a number of studies of different types of vaccines, combinations of substrates that may take into account more variance at the same time. And we’ll have the results of those studies in hand soon. And there was agreement in the committee that we should try to reach a consensus and have all the manufacturers use the same basic strategy so that we give it our very best shot, much like what we do with a flu vaccine. So, you know, the short answer is yes, or is likely to be a different vaccine in the fall, we hope it’ll be more sustained and more.

Andy Slavitt

That’s a decision. It sounds like the committee recommended gets made sometime in June. Is that about right?

Robert Califf 

Sometime over the summer, I’d say I don’t want to be too aggressive about giving dates.

Andy Slavitt  32:56

Sure. And then there’s a small matter of Congress having to give us money to buy more vaccines, if there is a different a new vaccine. So get ready to spend some of those summer and fall in front of Congress telling them why they need to re up their commitment to the pandemic. That is not over yet.

Robert Califf

Well, Andy, this is in your bailiwick. I wish you had solved the problem when you were in the seat. But you know, the worry, as you well know is that if this is not public, it’s not funded as a public health measure. We’re going to recapitulate all the problems we have in our health system where the well to do and highly educated will be getting their treatment, and those without means will have a much more difficult time. And I hope we don’t do it that way for a public health issue like this.

Andy Slavitt 

It’s right, in the self-interest of the well to do in Congress with an infectious disease or a recipe for let’s not vaccinate the people who can’t afford it doesn’t seem like a great recipe.

Robert Califf 

I certainly wouldn’t recommend it for my neighborhood.

Andy Slavitt  34:04

How about other vaccine types? Maybe on the not on the immediate horizon, but that we should be aware of and should be thinking of besides the mRNA? Are there hope for oral nasal other type of breakthroughs in the future that you think hold some promise?

Robert Califf

People are working on all those different variations, I mean, the one that is on the near-term horizon is a few more cell-based vaccines, not the messenger RNA type. And you’ll be seeing a lot more about that shortly.

Andy Slavitt 

Can you explain to us what that means what the impact of that is?

Robert Califf 

Just think of it as more like the way vaccines have been made in the past. We have several versions which are being used in other parts of the world, which are putting in their FDA applications now, which as I’ve already said, you know, there’s a different level of rigor at FDA in terms of independent analysis of the data and such. Those are coming up shortly. And we have, you know, I hear from people who don’t want to take the messenger RNA for one reason or another, and in whom these vaccines could be useful and appropriate.

Andy Slavitt 

You mean because of the microchip?

Robert Califf 

Well, yeah, I hope we’ll talk a little bit about misinformation because this is something we’ve got to focus on.

Andy Slavitt 

Let’s talk about misinformation. But I also will maybe just hit update on therapeutics. First of all, how do you feel about what you’re hearing about how remdesivir is doing? And then beyond that, is there a portfolio of additional therapeutics that you see around the horizon that could be as effective or even better?

Robert Califf

Well, I mean, it breaks my heart. And, you know, again, it also puts the anxiety of parents of young children in perspective, and makes it very understandable. But if you think about it this way, you get vaccinated, your chances of dying from COVID are reduced by 90%. If you’re unlucky enough to get infected, even though you’re vaccinated, if you get an antiviral, your risk of dying is reduced by yet another 90%. Now, most people listening are probably not mathematicians. But this is a contingent probability, it means that almost no one should be dying from COVID at this point, if we optimally deploy vaccination and antivirals, so it’s a tragedy, whenever a person dies from COVID, because we have highly effective treatments, and now in our antiviral portfolio, as you’ve alluded to, we have several options which are effective, and they’re more on the way, so we’re gonna get better and better. But our deployment is suboptimal.

Andy Slavitt  36:55

It’s exciting. I mean, that soundbite of almost no one should be dying of COVID. It looks incredible, incredible vote of confidence, science and research. And as you said, planning and investing in basic science for years and decades, just have to be at that spot, be able to say that, there’s remarkable there’s a lot of horrible things we can say about the pandemic and a lot of grief and trauma. But that’s wonderful to be able to hear, how about long COVID, do you think that there are, you know, we are hearing certainly that vaccines. We had some experts on COVID, who’ve done some analysis who were on the show and said that long COVID likelihood is cut in half if people are vaccinated. And that’s even the case if you get vaccinated immediately after getting infected. Are we working on potentially some on label answers for people who are suffering from long COVID? Do we think that’s a realistic target?

Robert Califf 

Well, we’re gonna find out, you know, the NIH is doing a huge study of long COVID and others are at work now, we need to get more practical and pay attention to this and have a better systematic approach to testing treatments. But if vaccination works, or antivirals work, that’s another theme that you hear but not yet definitive. It’ll be authorized just like any other treatment, we have to take long COVID Seriously, the MRI study from the UK showing the damage that’s done to the brain, not to mention other elements.

Andy Slavitt

Can you explain what that study showed for those who haven’t seen it?

Robert Califf  38:35

So this is a study that from the UK Biobank. So it’s a systematic evaluation of hundreds of 1000s of people in Britain adults. And they did something that because they have the ongoing study was serial images of the brain. They simply looked at people who got infected and those who didn’t, and these are mild infections. And there was a very detectable effect in terms of destroying parts of the brain now. And, you know, because you know, the loss of sense of smell and taste that those parts of the brain were most affected in the study. But so were areas like the frontal cortex, where our ability to think and reason occurs. Now, it’s not known whether these are going to be permanent effects, and they’re not enormous, but it’s enough to make one worry and to validate the people who say, you know, I have this foggy brain months after I had COVID. This is not just someone obsessing, it’s likely to be an actual effect of the infection.

Andy Slavitt 

Yeah, it also sounds like venturing into your work that might because I don’t I’m not a scientist, but the vagus nerve was the other thing that we’ve been hearing about, from one of the guests on the show that that the vagus nerve is impaired to the point where it impacts a lot of kind of normal body functions. The good news there is that they’ve been able to identify some rehabilitation steps and some lifestyle changes that can restore some functionality and reduce symptoms.

Andy Slavitt

Yeah, I completely agree. And, you know, as a cardiologist, we’ve known a long time that the brain and heart and the vascular system are all connected. So we have all set of compensations. If we just stand up, you know, out of a chair, our blood pressure would drop unless our blood vessels constricted, and when the vagus nerve is not functioning, right, people can pass out when they stand up, which can be quite dangerous. So this dysautonomia is called is a real thing. I think you had a session on this, it was quite good.

Andy Slavitt

So how far are we do you think we are from seeing some long COVID treatments? Are we talking months? Are we talking years?

Robert Califf  40:53

I think if we have a breakthrough treatment, it’ll be months, I think much of it is likely to require a combination. You mentioned rehab and physical therapy and those sorts of things, which are not cures for the problem. So I think some combination therapies may be, you know, monster, a couple of years before we began to see proof of benefit.

Andy Slavitt 

So Rob, one of the things that you have been focused on since you’ve been back in the chair? And even before you get back in the chair, that we’ve talked about quite a bit is the effect of misinformation on our ability to manage things like this pandemic, and other health related issues, can you talk about that?

Andy Slavitt

Yeah, I’m really concerned about it, Andy, in fact, I can’t document this because there’s not a tally. But I’m arguing. My argument is with Congress that misinformation is the leading cause of death in America. Now, if you look at, you know, what we already talked about with regard to vaccines, you got something that’s 90% effective in preventing death, and yet a very large number of people are not up to date on their vaccinations.

Andy Slavitt  42:09

I mean, who do you look to and say, particularly in the that are purposely misleading the public?

Robert Califf

Well, I mean, it’s easy to point to the anti-vax movement, you know, they’re the names are easily ascertainable. But I think more important than that is what’s the counterforce? Because we do believe in the First Amendment, we believe in the freedom of speech. And the question is, how are we going to get our act together so that reliable, truthful sources outweigh and persuade the negative influences and I think right now, the most important thing, are is person to person interaction. So people do trust their nurse practitioner, their doctor, their pharmacist, and they interact with them, we just have to support the clinical workforce in a different way, and help them get armed to combat this, you know, I was a practicing doc for three and a half decades, and it never crossed my mind that my 15-minute clinic interaction with a person would be completely outweighed by the next three months’ worth of social media and stuff on that they get exposed to. So we got to think differently in this new information environment and persuade people with good, useful, practical, reliable, understandable information that outweighs and outperforms the negative information they’re exposed to every day.

Andy Slavitt

Well, there’s a lot of things we didn’t get to talk about. There’s a lot that the FDA does every day to news. Regulating tobacco is something that we talk about Alzheimer’s, in the search for a cure, food inspection, massive amount of work that your colleagues at the FDA are responsible for every day that most people never get a chance to see. And so we get a chance to do that another time. We’d love to have you back and talk about some of those other topics.

Robert Califf 

Yeah, I really hope we can you know, I’m preparing for the budget hearing something that I know you grew to love tremendously, where members of Congress can ask you about anything they want, you’re there to defend the budget, but so I’ve gotten re-expose to the entire portfolio of 25% of the economy. And there are some amazing topics but we there’s some things we better take seriously that I hope we can talk about soon because I think your listeners would benefit from thinking about them, maybe some things I hadn’t thought about. Because what you’ve discovered today is mostly what’s in the headlines and on the front of people’s minds.

Andy Slavitt  44:57

Well, if you’re willing, I’d love to do that. Have you come back and just deliver those that budget meeting. I’m sure there’s a lot of messages to deliver to Congress as well, because they may have questions, but they’ve got a role to play in getting us the rest of the way, not just quite frankly, with the pandemic. But in ensuring that some of these other solutions that we talked about at the very beginning of this program, can see the light, see reality and save people’s lives. Rob, thank you, I won’t keep you any longer. I always love talking to you, and really appreciate you being in the bubble.

Robert Califf

Alright, it’s fun talking take care.

Andy Slavitt 

Okay, I hope that you enjoyed that interview with Rob Califf. If you’re a first-time listener in the bubble, go back and listen to some earlier episodes. There’s some fun ones in there. And we enjoy bringing them to you. Let me give you a kind of a quick interpretation of that interview, in my view, take stock in the literal words that he said. And I think Rob is extraordinarily thoughtful about what he says and how he says it. But I’m going to try to string a few things he said together to make sure they’re well understood. Rob, as a political appointee, as by the way I was when I was in the government both times is not permitted to make the decision around the approval of a drug or medication. And that’s done to protect against people who are meant to make political decisions. And it’s really career scientists that make these decisions about approval or not approval. So you think that I could say, Rob, because you run the FDA, Hey, Rob, when is this gonna get approved. And because he’s charged, he could tell me the date. But it’s actually Peter Marks who we had on the show a couple of weeks back, and his team that are doing the work. And Rob’s job, Rob’s number one job was to protect Peter Marks’ team, the FDA scientists against political interference against interference from the outside and to allow them to do their job as a deterrent. Their jobs are very simply to review the safety data, and the efficacy data almost with blinders on. And Rob’s job is to absorb and take away the political heat. So you’re not going to hear in an interview of you expected to Rob Califf saying this is when it’s going to be approved, or this is when it’s going to be reviewed. So knowing that, and you hear Rob, effectively, saying what he said in this episode, and we played at the beginning, the code is the Siemens going to act with great haste. Now, I don’t know when the Pfizer application comes in. But what I will tell you is the Pfizer vaccine submissions already been partially reviewed. And so that maybe will be done more quickly. And they will have what’s called the VERB[…]  meeting, which is there outside advisers to discuss the results. And it’s possible that if the Pfizer application comes in quickly, and the signal is from Pfizer, that it’ll come in in the next two weeks. And that’s a three-dose vaccine, it’s possible that they can get that done in the same meeting, given that it’ll take a little longer to review Moderna.

Andy Slavitt  48:13

But what he’s not saying is that he’s going to wait for the Pfizer vaccine submission. And if the Pfizer vaccines submission terms, and after they’ve had a chance to review, Moderna that it sounded to me, like he was saying, we’re gonna get this approved as soon as possible, or we need to be reviewed as soon as possible. And he reminded us several times in the interview, that he hadn’t seen the data yet, and that there was no data. And that while everyone’s waiting, in some cases patiently, in some cases, impatiently, they can’t do anything until they seen the data now that Moderna sent them the application the balls in their court, now they’ve got a chance to review it. It is normally a several week process to review an application, you might know that Moderna does not have a vaccine approved already or authorized for kids, five to 11. So there is probably a more foundational kind of review necessary. But what I was listening for, was is FDA going to act with urgency to review this and get it approved as quickly as possible. That’s what I heard. We also you recall, asked the question of if the vaccine is not meet the threshold of 50% effectiveness, would they still approve it? And that’s important, because it gives Omicron the vaccines are much less effective. And so that 50% approval, that 50% Number is kind of different meeting today. And I think what he said and in fact, should give comfort that if they’re under 50%, as Madonna had indicated prior to the submission, that that’s not going to stop them from getting approval. So that’s my interpretation. And I just wanted to add kind of my decoder ring to this as far as I can interpret, but again, his literal words were chosen quite carefully, I thought that he was quite forthcoming about his forthcoming really allowed to be when you’re in the situation he’s in where you don’t make the actual decision. But in fact, you have to make sure that the scientists get an opportunity to make the decisions done if you felt the same way. But I did. I really respect Rob for coming on and being so frank, and more than that, I thought he was incredibly thoughtful about all the topics we discussed. But as you know, he’s a friend of mine. So take that was a grain of salt if you choose. It’s okay to be cynical. That’s why I disclose our friendship.

Andy Slavitt

Okay. Now we’re talking about what’s coming up on future episodes. This was our Monday episode of next week. So on Monday, you should listen to this again. But we will still have two more shows next week. Because we are kicking our first three episodes a week IN THE BUBBLE. Oh, my goodness. Are we crazy? Let us know if you think we’re crazy Wednesday Joneigh Khaldun. We’re talking about health equity. And then our first Friday show, we are going to have on in the bubble, in depth roundtable discussion with some great guests on a topic that I think is getting a lot of play in the news, which is this clash of free speech, media owned by billionaires, journalism, and the fight to get disinformation versus real information out to people that’s all being bagged, of course, by that guy, Elon Musk, who is acquiring Twitter, but I will have you know, this is getting started here. First Elan Musk is not acquiring this podcast, at least as far as I know. Okay. All right. That’ll be a fun episode. And then following that, Deborah Birx. From the Trump administration. Yes, that Deborah Birx. Okay, folks, have a great weekend and play this again on Monday will ya?

Andy Slavitt  52:14

Thanks for listening to IN THE BUBBLE. We’re a production of Lemonada Media. Kathryn Barnes, Jackie Harris and Kyle Shiely produced our show, and they’re great. Our mix is by Noah Smith and James Barber, and they’re great, too. Steve Nelson is the vice president of the weekly content, and he’s okay, too. And of course, the ultimate bosses, Jessica Cordova Kramer and Stephanie Wittels Wachs, they executive produced the show, we love them dearly. Our theme was composed by Dan Molad and Oliver Hill, with additional music by Ivan Kuraev. You can find out more about our show on social media at @LemonadaMedia where you’ll also get the transcript of the show. And you can find me at @ASlavitt on Twitter. If you like what you heard today, why don’t you tell your friends to listen as well, and get them to write a review. Thanks so much, talk to you next time.

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